With reference to FIGS. 1 and 2, which depict the male urogenital anatomy 10, the prostate 20 is a complex, walnut-sized gland in the male urogenital anatomy 10 that is located just below the bladder 22. The walls 23 of the bladder 22 relax and expand to store urine and contract and flatten to empty urine through the urethra 28, which extend from the bladder 23, through the prostate 20, and to the end of the penis 24.
The part of the urethra 28 that is surrounded by the prostate 20 is referred to as the prostatic segment of the urethra, or prostatic urethra. The prostate 20 also surrounds the ejaculatory ducts 25 where they enter the prostatic urethra 28. During sexual excitement, the sperm leave the epididymis 27 (which is attached to the surface of the testis) and is carried by the ductus deferens 29 in the direction of the prostate 20. A primary function of the prostate 20 is to supply nutritional fluid for the sperm to form semen during ejaculation. This fluid, which is produced in the seminal vesicles 21 (see FIG. 2) is added to the semen during ejaculation. On each side, the ductus deferens 29 and seminal vesicle 21 join to form a single tube called the ejaculatory duct 25. Each ejaculatory duct 25, left and right, carries the seminal vesicle secretion and sperm through the prostate gland 20, emptying into the prostatic urethra 28.
According to a typical model of the prostate, four different anatomical zones may be distinguished, which have anatomo-clinical correlation: (1) The peripheral zone 1, which is the area forming the postero-inferior aspect of the gland. It represents 70% of the prostatic volume, and is the zone where the majority (60-70%) of prostate cancers form. (2) The central zone 2, which represents 25% of the prostate volume and through which the ejaculatory ducts pass. This is the zone which usually gives rise to inflammatory processes (e.g., prostatitis). (3) The transitional zone 3, which represents only 5% of the total normal prostatic volume and is the zone where benign prostatic hypertrophy occurs. It consists of two lateral lobes together with periurethral glands. Approximately 25% of prostatic adenocarcinomas also occur in this zone. (4) The anterior zone 4, which is predominantly fibromuscular.
The prostate 20 weighs approximately 20 g by the age of 20 and has the shape of an inverted cone, with the base at the bladder neck and the apex at the urogenital diaphragm. The prostatic urethra 28 does not follow a straight line as it runs through the center of the prostate gland 20 but it is actually bent anteriorly near the point where the ejaculatory ducts joins the prostate.
A significant portion of the male populace sooner or later faces complaints related mostly, although not exclusively, to the increased size of the prostate gland, known as benign prostate hypertrophy (“BPH”). The predominant symptoms of BPH are an increase in frequency and urgency of urination, as well as retention of urine in the bladder, which eventually can lead to complete inability to urinate. The condition significantly alters the quality of life. Moreover, urinary retention inevitably leads to lower urinary tract infection (“LUTI”). The LUTI then ascends into the kidneys causing chronic pyelonephritis, which eventually leads to renal insufficiency and death, unless the cause (i.e., the BPH and its associated urine retention) is eliminated or at least abated. With the aging of the male population, this scenario is becoming more and more frequent.
BPH is the consequence of the disturbed balance between the continuous production and natural death (apoptosis) of the glandular cells of the prostate. Overwhelming cell production leads to increased prostate size and dislodgement/engorgement of the urinary tract segment, which traverses the prostatic gland (i.e., prostatic urethra). The cause of the disturbed balance is thought to be the dihydrotestosterone (DHT), an enzymatically converted form of the male hormone, testosterone. This hormone is the dominant male hormone in the adult prostate. It forms a complex with the androgen receptors. The complex enters the nuclei of the cells, and maintains and extends cell proliferation and prevents apoptosis.
In mild cases of BPH, medical treatment can alleviate the symptoms for some period of time. For example, alpha-adrenergic blockers (e.g. Hytrin), which relax the smooth muscle cell components of the prostate, can be effective until the glandular elements become overwhelming in the organ. Moreover, the enzyme blocker, finasteride, which prevents DHT production, also alleviates the complaints in about half of the cases but only after 6 months of oral treatment.
Advanced cases of BPH, however, can only be treated by mechanical or physical interventions such as transurethral physical destruction of prostatic tissue, for example using mechanical fragmentation, heat, cryosurgery, congelation, and so forth. These interventions often give only transient relief, at the expense of significant peri-operative discomfort and morbidity. A common prostate surgery involves trans-urethral resection of the prostate (TURP), which is accomplished by resecting the prostatic tissues surrounding the urethra that cause obstruction. Unfortunately, although effective in reducing obstructions, the dominant mechanism behind TURP is the progressive coring-out of the prostate, beginning at the level of the urethra and progressing outward into the prostatic capsule. Hence, this surgical procedure is destructive to the urethra and carries various complications including urinary incontinence, retrograde ejaculation, and impotence. Moreover, there is a high recurrence rate.
Another treatment modality employed is the surgical removal of the prostate (prostatectomy). It is a more definite solution, but it is a major surgery, is often associated with high morbidity and fairly high mortality, and often leads to severe sexual dysfunction.
Prostate cancer is the leading cancer diagnosis and the second most common cancer-related cause of death in men in the USA. It is the fourth most common malignancy worldwide. There has been a dramatic increase in the annual incidence: from 2.3% between 1975 and 1985 to 14% between 1992 and 1995 (Surveillance, Epidemiology and End Result program of the National Cancer Institute). The mortality rate, however, has undergone a slight decrease since 1995.
Several techniques are currently practiced for the treatment of prostate cancer, including the following: (1) Radical (anatomic retropubic or perineal) prostatectomy, which is a major intervention with high morbidity (e.g., thromboembolic and bleeding complications, erectile dysfunction, etc.) and fairly high mortality. (2) Radiation therapy, for example, three dimensional conformal high energy beam radiation (neutron or proton), with or without intensity modulation. It is an expensive procedure, its effectiveness has not yet been proven in randomized studies, and the procedure often leads to urethral strictures. (3) Brachytherapy, which involves the delivery, via an elaborate transperineal insertion procedure, of radioisotope seeds deep into the prostate tissue under ultrasound or MRI guidance. It is a lengthy operation under anesthesia, with high complication rates. (4) Systemic androgen suppression, which is objected to by many, especially in early stages of the cancer, due to feminization and erectile dysfunction. (5) Therapy with (neo)adjuvant agents, many of which are either proteins or polynucleotides, and therefore cannot be applied systemically due to the body's degradation processes.
Since an effective cancer therapy requires a minimum of five years, disease-free survival, there simply is not enough experience to know the efficacy of many of the newest therapeutic modalities. Nonetheless, a number of disadvantages of the current treatment methods are known as indicated above.
Inflammatory disease of the prostate (prostatitis) is the most important disease of the prostate after BPH and cancer. It is the most common urologic diagnosis in men younger than 50 years and the third most common in men older than 50 years. Prostatitis results in around 2 million office visits per year in the USA, corresponding to 8% of the total urology office visits. This condition significantly interferes with the quality of life due to constant pain (prostodynia) and urethral discharge. Well selected antibiotic treatment can eradicate the acute bacterial infection in most of the cases. However, the success rate with chronic prostatitis ranges from 0% to 67%, very often with an associated 90-day treatment period and high recurrence rate. This is partially due to the relative isolation of the prostate gland from the circulation, both anatomically as well as pharmacokinetically (e.g., acidic antibiotics have difficulty penetrating the alkaline prostatic acini).
Hence, present medical treatments are insufficient, lengthy and/or expensive, and the search for more effective, less invasive methods having less discomfort, longer lasting results and less expense continues.